精准调控Baeyer-Villiger单加氧酶的底物选择性以避免拉唑亚砜的过氧化

doi:10.1016/S1872-2067(23)64482-1

催化学报 ›› 2023, Vol. 51: 157-167.DOI: 10.1016/S1872-2067(23)64482-1

精准调控Baeyer-Villiger单加氧酶的底物选择性以避免拉唑亚砜的过氧化

吴殷琦^a^,¹, 陈倩倩^b^,¹, 陈琦^a^,¹, 耿强^a, 张巧玉^b, 郑宇璁^a, 赵晨^a, 张龑^a, 周佳海^c, 王斌举^b^,^*(), 许建和^a^,^*(), 郁惠蕾^a^,^*()

^a华东理工大学生物反应器工程国家重点实验室, 上海生物制造协同创新中心, 上海200237
^b厦门大学化学化工学院, 固体表面物理化学国家重点实验室, 福建省理论与计算化学重点实验室, 福建厦门361005
^c中国科学院深圳先进技术研究院, 深圳合成生物研究所, 中国科学院定量工程生物学重点实验室, 广东深圳518055

收稿日期:2023-04-22 接受日期:2023-06-20 出版日期:2023-08-18 发布日期:2023-09-11
通讯作者: *电子信箱: huileiyu@ecust.edu.cn (郁惠蕾), jianhexu@ecust.edu.cn (许建和), wangbinju2018@xmu.edu.cn (王斌举).
作者简介:第一联系人：¹共同第一作者.
基金资助:
国家自然科学基金(21922804);国家自然科学基金(32271540);国家自然科学基金(31971380);国家自然科学基金(22122305);国家重点研发计划(2019YFA0905000);国家重点研发计划(2021YFC2102900);上海市学术带头人项目(21XD1400800);中央高校基本研究经费专项资金(22221818014)

Precise regulation of the substrate selectivity of Baeyer-Villiger monooxygenase to minimize overoxidation of prazole sulfoxides

Yinqi Wu^a^,¹, Qianqian Chen^b^,¹, Qi Chen^a^,¹, Qiang Geng^a, Qiaoyu Zhang^b, Yu-Cong Zheng^a, Chen Zhao^a, Yan Zhang^a, Jiahai Zhou^c, Binju Wang^b^,^*(), Jian-He Xu^a^,^*(), Hui-Lei Yu^a^,^*()

^aState Key Laboratory of Bioreactor Engineering and Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
^bState Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, China
^cCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China

Received:2023-04-22 Accepted:2023-06-20 Online:2023-08-18 Published:2023-09-11
Contact: *E-mail: huileiyu@ecust.edu.cn (H.-L. Yu), jianhexu@ecust.edu.cn (J.-H. Xu), wangbinju2018@xmu.edu.cn (B. Wang).
About author:First author contact:¹Contributed equally to this work.
Supported by:
National Natural Science Foundation of China(21922804);National Natural Science Foundation of China(32271540);National Natural Science Foundation of China(31971380);National Natural Science Foundation of China(22122305);National Key Research and Development Program of China(2019YFA0905000);National Key Research and Development Program of China(2021YFC2102900);Program of Shanghai Academic Research Leader(21XD1400800);Fundamental Research Funds for the Central Universities(22221818014)

摘要/Abstract

摘要：

氧化酶催化的分子功能化是非常具有吸引力的研究领域之一,其中,高度选择性氧化反应对手性分子的构建至关重要.大量研究集中在对氧化酶立体选择性和区域选择性的分子改造上,而由于底物选择性差引起的过度氧化问题长期被忽视.Baeyer-Villiger单加氧酶(BVMOs)是一类多功能的生物催化剂,可以在脂肪族或环状酮底物的羰基附近插入一个氧原子,具有较高的区域选择性.BVMOs还可以催化包括硫、氮和磷在内的杂原子的不对称氧化.由于其温和的反应条件和较好的对映选择性,BVMOs催化硫醚不对称氧化生成手性亚砜被认为是一种极具吸引力且绿色清洁的合成方法.
BVMOs可以催化硫醚不对称氧化生成有价值的手性亚砜,但亚砜过氧化生成无用的副产物砜限制了其进一步应用.这种过度氧化的本质原因是BVMOs对底物选择性不足,导致目标产物亚砜被进一步氧化.本文建立了一个数学模型,将酶对硫醚和亚砜两种相似底物之间的特异性常数之比(k_cat/K_m)定义为酶对底物选择性.随后使用蛋白结构引导的底物通道工程方法精准调控了拉唑硫醚单加氧酶AcPSMO的底物选择性,成功地将亚砜的过氧化降至最低.酶促氧化奥美拉唑硫醚24h后,突变体F277L生成的副产物砜含量低于1%(mol/mol),而野生型的砜含量为65%.分子动力学模拟和量子力学/分子力学研究结果表明,黄素氢过氧化物(FADH-OOH)周围改变的氢键网络可以调节亚砜氧化的机制和活性.此外,重新设计的AcPSMO突变体也成功地应用于其它手性拉唑亚砜的可控合成.综上,本文开发的精确控制氧化酶底物选择性的方法对于提高其它杂原子生物氧化反应的底物特异性具有借鉴意义.

关键词: Baeyer-Villiger单加氧酶, 手性亚砜, 过度氧化, 底物选择性, 蛋白质工程, 分子动力学模拟, 量子力学/分子力学研究

Abstract:

Baeyer-Villiger monooxygenases (BVMOs) can catalyze the asymmetric oxidation of sulfides to valuable chiral sulfoxides, but the overoxidation of sulfoxides to undesired sulfones limits the synthetic application of BVMOs. This overoxidation is caused by insufficient substrate selectivity of BVMOs, where the desired product sulfoxide can be further oxidized. In this study, a mathematical model was constructed to quantitatively define the substrate selectivity based on the ratio of the specificity constant (k_cat/K_m) between sulfide and sulfoxide. The substrate selectivity of a pyrmetazole monooxygenase (AcPSMO) was precisely regulated using a structure-guided substrate tunnel engineering approach, which successfully minimized sulfoxide overoxidation. The sulfone content of variant F277L was less than 1% (mol/mol), compared with 65% for the wild-type, in the pyrmetazole oxidation reaction after 24 h. Molecular dynamics simulations and quantum mechanics/molecular mechanics studies showed that the altered H-bonding networks surrounding the flavin hydroperoxide (FADH-OOH) can modulate the mechanism and activity for sulfoxide oxidation. Furthermore, the redesigned mutants of AcPSMO were successfully applied for the controllable synthesis of other chiral prazole sulfoxides.

Key words: Baeyer-Villiger monooxygenase, Chiral sulfoxide, Overoxidation, Substrate selectivity, Protein engineering, Molecular dynamics simulation, Quantum mechanics/molecular, mechanics study

吴殷琦, 陈倩倩, 陈琦, 耿强, 张巧玉, 郑宇璁, 赵晨, 张龑, 周佳海, 王斌举, 许建和, 郁惠蕾. 精准调控Baeyer-Villiger单加氧酶的底物选择性以避免拉唑亚砜的过氧化[J]. 催化学报, 2023, 51: 157-167.

Yinqi Wu, Qianqian Chen, Qi Chen, Qiang Geng, Qiaoyu Zhang, Yu-Cong Zheng, Chen Zhao, Yan Zhang, Jiahai Zhou, Binju Wang, Jian-He Xu, Hui-Lei Yu. Precise regulation of the substrate selectivity of Baeyer-Villiger monooxygenase to minimize overoxidation of prazole sulfoxides[J]. Chinese Journal of Catalysis, 2023, 51: 157-167.

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参考文献

[1]	Y. J. Liang, J. L. Wei, X. Qiu, N. Jiao, Chem. Rev., 2018, 118, 4912-4945.
[2]	S. N. Charlton, M. A. Hayes, ChemMedChem, 2022, 17, e202200115.
[3]	S. C. Dodani, G. Kiss, J. K. B. Cahn, Y. Su, V. S. Pande, F. H. Arnold, Nat. Chem., 2016, 8, 419-425.
[4]	G. Y. Li, M. Garcia-Borras, M. J. L. J. Furst, A. Ilie, M. W. Fraaije, K. N. Houk, M. T. Reetz, J. Am. Chem. Soc., 2018, 140, 10464-10472.
[5]	C. G. Acevedo-Rocha, C. G. Gamble, R. Lonsdale, A. T. Li, N. Nett, S. Hoebenreich, J. B. Lingnau, C. Wirtz, C. Fares, H. Hinrichs, A. Deege, A. J. Mulholland, Y. Nov, D. Leys, K. J. McLean, A. W. Munro, M. T. Reetz, ACS Catal., 2018, 8, 3395-3410.
[6]	C. Gally, B. M. Nestl, B. Hauer, Angew. Chem. Int. Ed., 2015, 54, 12952-12956.
[7]	R. J. Li, A. T. Li, J. Zhao, Q. Chen, N. Li, H. L. Yu, J. H. Xu, Catal. Sci. Technol., 2018, 8, 4638-4644
[8]	B. P. Branchaud, C. T. Walsh, J. Am. Chem. Soc., 1985, 107, 2153-2161.
[9]	M. Renz, M. Bernard, Eur. J Org. Chem., 1999, 737-750.
[10]	M. D. Mihovilovic, B. Müller, P. Stanetty, Eur. J. Org. Chem., 2002, 3711-3730.
[11]	H. Leisch, K. Morley, P. C. K. Lau, Chem. Rev., 2011, 111, 4165-4222.
[12]	J. L. Han, V. A. Soloshonok, K. D. Klika, J. Drabowicz, A. Wzorek, Chem. Soc. Rev., 2018, 47, 1307-1350.
[13]	E. Romero, J. R. G. Castellanos, G. Gadda, M. W. Fraaije, A. Mattevi, Chem. Rev., 2018, 118, 1742-1769.
[14]	M. J. L. J. Furst, A. Gran-Scheuch, F. S. Aalbers, M. W. Fraaije, ACS Catal., 2019, 9, 11207-11241.
[15]	S. Schmidt, U. T. Bornscheuer, Chapter Nine, Enzymes, 2020, 47, 231-281
[16]	C. E. Paul, D. Eggerichs, A. H. Westphal, D. Tischler, W. J. H. van Berkel, Biotechnol. Adv., 2021, 51,107712
[17]	T. Matsui, Y. Dekishima, M. Ueda, Appl. Microbiol. Biotechnol., 2014, 98, 7699-7706.
[18]	I. Fernandez, N. Khiar, Chem. Rev., 2003, 103, 3651-3706.
[19]	Y. Zhang, Y. Q. Wu, N. Xu, Q. Zhao, H. L. Yu, J. H. Xu, ACS Sustainable Chem. Eng., 2019, 7, 7218-7226.
[20]	K. Balke, A. Beier, U. T. Bornscheuer, Biotechnol. Adv., 2018, 36, 247-263.
[21]	M. L. Mascotti, M. J. Ayub, H. Dudek, M. K. Sanz, M. W. Fraaije, AMB Express, 2013, 3, 33.
[22]	F. Liu, C. Shou, Q. Geng, C. Zhao, J. H. Xu, H. L. Yu, Appl. Microbiol. Biotechnol., 2021, 105, 3169-3180.
[23]	S. Bordewick, A. Beier, K. Balke, U. T. Bornscheuer, Enzyme Microbial. Technol., 2018, 109, 31-42.
[24]	M. T. Reetz, F. Daligault, B. Brunner, H. Hinrichs, A. Deege, Angew. Chem. Int. Ed., 2004, 43, 4078-4081.
[25]	F. M. Ferroni, M. S. Smit, D. J. Opperman, J. Mol. Catal. B, 2014, 107, 47-54.
[26]	Z. G. Zhang, R. Lonsdale, J. Sanchis, M. T. Reetz, J. Am. Chem. Soc., 2014, 136, 17262-17272.
[27]	C. C. Ryerson, D. P. Ballou, C. Walsh, Biochemistry, 1982, 21, 2644-2655
[28]	J. A. Latham, C. Walsh, J. Am. Chem. Soc., 1987, 109, 3421-3427.
[29]	C. Walsh, J. Latham, J. Protein Chem., 1986, 5, 79-87.
[30]	D. W. Sheng, D. P. Ballou, V. Massey, Biochemistry, 2001, 40, 11156-11167.
[31]	I. A. Mirza, B. J. Yachnin, S. Wang, S. Grosse, H. Bergeron, A. Imura, H. Iwaki, Y. Hasegawa, P. C. K. Lau, A. M. Berghuis, J. Am. Chem. Soc., 2009, 131, 8848-8854.
[32]	B. J. Yachnin, T. Sprules, M. B. McEvoy, P. C. K. Lau, A. M. Berghuis, J. Am. Chem. Soc., 2012, 134, 7788-7795.
[33]	I. Polyak, M. T. Reetz, W. Thiel, J. Am. Chem. Soc., 2012, 134, 2732-2741.
[34]	D. E. Torres Pazmino, B. J. Baas, D. B. Janssen, M. W. Fraaije, Biochemistry, 2008, 47, 4082-4093.
[35]	J. Sucharitakul, T. Wongnate, P. Chaiyen, J. Biol. Chem., 2011, 286, 16900-16909.
[36]	T. C. Bruice, J. B. Noar, S. S. Ball, U. V. Venkataram, J. Am. Chem. Soc., 1983, 105, 2452-2463.
[37]	A. C. C. Barbosa, R. P. P. Neves, S. F. Sousa, M. J. Ramos, P. A. Fernandes, ACS Catal., 2018, 8, 9298-9311.
[38]	N. Xu, J. Zhu, Y. Q. Wu, Y. Zhang, J. Y. Xia, Q. Zhao, G. Q. Lin, H. L. Yu, J. H. Xu, Org. Process Res. Dev., 2020, 24, 1124-1130.
[39]	Y. K. Bong, M. D. Clay, S. J. Collier, B. Mijts, M. Vogel, X. Zhang, J. Zhu, J. Nazor, D. Smith, S. Song, WO Patent, WO2011071982A2, 2011.
[40]	Y. K. Bong, S. Song, J. Nazor, M. Vogel, M. Widegren, D. Smith, S. J. Collier, R. Wilson, S. M. Palanivel, K. Narayanaswamy, B. Mijts, M. D. Clay, R. Fong, J. Colbeck, A. Appaswami, S. Muley, J. Zhu, X. Zhang, J. Liang, D. Entwistle, J. Org. Chem., 2018, 83, 7453-7458.
[41]	O. Trott, A. J. Olson, J. Comput. Chem., 2010, 31, 455-461.
[42]	H. Li, A. D. Robertson, J. H. Jensen, Proteins: Struct., Funct., Bioinform., 2005, 61, 704-721.
[43]	D. A. Case, I. Y. Ben-Shalom, S. R. Brozell, D. S. Cerutti, T. E. Cheatham, III, V. W. D. Cruzeiro, T. A. Darden, R. E. Duke, D. Ghoreishi, M. K. Gilson, H. Gohlke, A. W. Goetz, D. Greene, R. Harris, N. Homeyer, Y. Huang, S. Izadi, A. Kovalenko, T. Kurtzman, T. S. Lee, S. LeGrand, P. Li, C. Lin, J. Liu, T. Luchko, R. Luo, D. J. Mermelstein, K. M. Merz, Y. Miao, G. Monard, C. Nguyen, H. Nguyen, I. Omelyan, A. Onufriev, F. Pan, R. Qi, D. R. Roe, A. Roitberg, C. Sagui, S. Schott-Verdugo, J. Shen, C. L. Simmerling, J. Smith, R. SalomonFerrer, J. Swails, R. C. Walker, J. Wang, H. Wei, R. M. Wolf, X. Wu, L. Xiao, D. M. York, P. A. Kollman, AMBER 2018, University of California, San Francisco, 2018.
[44]	J. M. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman, D. A. Case, J. Comput. Chem., 2004, 25, 1157-1174.
[45]	C. I. Bayly, P. Cieplak, W. D. Cornell, P. A. Kollman, J. Phys. Chem., 1993, 97, 10269-10280.
[46]	W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey, M. L. Klein, J. Chem. Phys., 1983, 79, 926-935.
[47]	J. A. Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, K. E. Hauser, C. Simmerling, J. Chem. Theory Comput., 2015, 11, 3696-3713.
[48]	C. L. Brooks III, J. Solution Chem., 1989, 18, 99.
[49]	W. F. van Gunsteren, H. J. C. Berendsen, Angew. Chem. Int. Ed., 1990, 29, 992-1023.
[50]	V. Kräutler, W. F. van Gunsteren, P. H. Hünenberger. J. Comput. Chem., 2001, 22, 501-508.
[51]	P. Sherwood, A. H. de Vries, M. F. Guest, G. Schreckenbach, C. R. A. Catlow, S. A. French, A. A. Sokol, S. T. Bromley, W. Thiel, A. J. Turner, S. Billeter, F. Terstegen, S. Thiel, J. Kendrick, S. C. Rogers, J. Casci, M. Watson, F. King, E. Karlsen, M. Sjøvoll, A. Fahmi, A. Schäfer, C. Lennartz, J. Mol. Struct.: Theochem., 2003, 632, 1-28.
[52]	R. Ahlrichs, M. Bar, M. Haser, H. Horn, C. Kolmel, Chem. Phys. Lett., 1989, 162, 165-169.
[53]	W. Smith, T. R. Forester, J. Mol. Graphics, 1996, 14, 136-141.
[54]	A. H. de Vries, P. Sherwood, S. J. Collins, A. M. Rigby, M. Rigutto, G. J. Kramer, J. Phys. Chem. B, 1999, 103, 6133-6141.
[55]	P. Sherwood, A. H. de Vries, S. J. Collins, S. P. Greatbanks, N. A. Burton, M. A. Vincent, I. H. Hillier, Faraday Discuss., 1997, 106, 79-92.
[56]	S. Grimme, J. Comput. Chem., 2004, 25, 1463-1473.
[57]	P. Wu, Y. Gu, L. Liao, Y. Wu, J. Jin, Z. Wang, J. Zhou, S. Shaik, B. Wang, Angew. Chem. Int. Ed., 2022, 61, e202214235.
[58]	W. Peng, S. Yan, X. Zhang, L. Liao, J. Zhang, S. Shaik, B. Wang, J. Am. Chem. Soc., 2022, 144, 20484-20494.
[59]	X. Zhang, Y. Jiang, Q. Chen, S. Dong, Y. Feng, Z. Cong, S. Shaik, B. Wang, ACS Catal., 2021, 11, 8774-8785.
[60]	J. Kaestner, J. M. Carr, T. W. Keal, W. Thiel, A. Wander, P. Sherwood, J. Phys. Chem. A, 2009, 113, 11856-11865.
[61]	C. S. Chen, Y. Fujimoto, G. Girdaukas, C. J. Sih, J. Am. Chem. Soc., 1982, 104, 7294-7299.
[62]	S. Zhu, Y. Wu, Z. Yu, Proc. Biochem., 2006, 41, 1688-1691.
[63]	W. R. Berendsen, G. Gendrot, S. Resnick, M. Reuss, J. Biotechnol., 2006, 121, 213-226.
[64]	E. Romero, J. R. G. Castellanos, A. Mattevi, M. W. Fraaije, Angew. Chem. Int. Ed., 2016, 55, 15852-15855.
[65]	D. Lim, K. Poole, N. C. J. Strynadka, J. Biol. Chem., 2002, 277, 29253-29259.
[66]	H. L. Messiha, S. T. Ahmed, V. Karuppiah, R. Suardiaz, G. A. Ascue Avalos, N. Fey, S. Yeates, H. S. Toogood, A. J. Mulholland, N. S. Scrutton, Biochemistry, 2018, 57, 1997-2008.
[67]	M. J. L. J. Fürst, S. Savino, H. M. Dudek, J. R. Gomez Castellanos, C. Gutierrez de Souza, S. Rovida, M. W. Fraaije, A. Mattevi, J. Am. Chem. Soc., 2016, 139, 627-630.
[68]	M. T. Reetz, B. Brunner, T. Schneider, F. Schulz, C. M. Clouthier, M. M. Kayser, Angew. Chem. Int. Ed., 2004, 43, 4075-4078.
[69]	K. Balke, S. Schmidt, M. Genz, U. T. Bornscheuer, ACS Chem. Biol., 2016, 11, 38-43.
[70]	M. D. Mihovilovic, F. Rudroff, A. Winninger, T. Schneider, F. Schulz, M. T. Reetz, Org. Lett., 2006, 8, 1221-1224.
[71]	S. Takahashi, Y. Zhao, P. E. O'Maille, B. T. Greenhagen, J. P. Noel, R. M. Coates, J. Chappell, J. Biol. Chem., 2005, 280, 3686-3696.
[72]	T. Yamazaki, T. Ohno, T. Sakaki, M. Akiyoshi-Shibata, Y. Yabusaki, T. Imai, S. Kominami, Biochemistry, 1998, 37, 2800-2806.
[73]	J. Carro, P. Ferreira, L. Rodriguez, A. Prieto, A. Serrano, B. Balcells, A. Arda, J. Jimenez-Barbero, A. Gutierrez, R. Ullrich, M. Hofrichter, A. T. Martine, FEBS J., 2015, 282, 3218-3229.

Enzyme	c^a (%)	ee ^b (S, %)	pp^a (%)	R_app^c
WT	98.7 ± 0.7	99.1	76.6 ± 1.8	12.6
L244V	62.1 ± 1.0	97.2	97.8 ± 0.2	25.2
F277V	93.2 ± 2.4	99.0	98.9 ± 0.2	170
F281V	95.1 ± 1.5	98.0	89.8 ± 1.1	20.1
L432V	83.8 ± 0.4	92.2	47.8 ± 0.7	1.44
A433V	97.7 ± 0.8	99.1	92.3 ±1.0	37.1

Enzyme	c^a (%)	ee ^b (S, %)	pp^a (%)	R_app^c
WT	98.7 ± 0.7	99.1	76.6 ± 1.8	12.6
L244V	62.1 ± 1.0	97.2	97.8 ± 0.2	25.2
F277V	93.2 ± 2.4	99.0	98.9 ± 0.2	170
F281V	95.1 ± 1.5	98.0	89.8 ± 1.1	20.1
L432V	83.8 ± 0.4	92.2	47.8 ± 0.7	1.44
A433V	97.7 ± 0.8	99.1	92.3 ±1.0	37.1

Enzyme	Pyrmetazole			(S)-Omeprazole
Enzyme	k_cat (min^‒1)	K_m (mmol/L)	k_cat/K_m (L min^‒1 mmol^‒1)	k_cat (min^‒1)	K_m (mmol L^‒1)	k_cat/K_m (L min^‒1 mmol^‒1)
L432V	0.42 ± 0.01	0.10 ± 0.01	4.39	3.77 ± 0.37	0.38 ± 0.07	9.93
WT	0.30 ± 0.01	0.20 ± 0.02	1.51	0.64 ± 0.01	0.85 ± 0.19	0.75
F277L	0.74 ± 0.09	0.14 ± 0.02	5.31	0.08 ± 0.00	1.70 ± 0.09	0.05

Enzyme	Pyrmetazole			(S)-Omeprazole
Enzyme	k_cat (min^‒1)	K_m (mmol/L)	k_cat/K_m (L min^‒1 mmol^‒1)	k_cat (min^‒1)	K_m (mmol L^‒1)	k_cat/K_m (L min^‒1 mmol^‒1)
L432V	0.42 ± 0.01	0.10 ± 0.01	4.39	3.77 ± 0.37	0.38 ± 0.07	9.93
WT	0.30 ± 0.01	0.20 ± 0.02	1.51	0.64 ± 0.01	0.85 ± 0.19	0.75
F277L	0.74 ± 0.09	0.14 ± 0.02	5.31	0.08 ± 0.00	1.70 ± 0.09	0.05

Substrate	Enzyme	c^a (%, 12 h)	pp^a (%)	R_app^b
Pymetazole	WT	51.9 ± 1.2	97.9 ± 0.1	78.3
	F277L	96.7 ± 0.6	98.9 ± 0.1	266
	D57Q	55.4 ± 1.1	98.7 ± 0.1	126
	F277L/D57Q	94.6 ± 0.1	99.1 ± 0.0	321
Lansoprazole sulfide	WT	58.7 ± 4.6	78.2 ± 1.7	7.53
	F277L	99.1 ± 0.0	97.2 ± 0.4	163
	F277L/D57Q	69.4 ± 1.7	97.6 ± 0.1	68.1
Pantoprazole sulfide	WT	99.9 ± 0.0	35.6 ± 1.1	7.36
	F277L	99.8 ± 0.0	95.3 ± 0.3	124
	F277L/D57Q	99.8 ± 0.0	96.7 ± 0.0	186
Ilaprazole sulfide	WT	75.2 ± 1.0	16.5 ± 0.4	2.00
	F277L	86.5 ± 0.1	93.1 ± 0.2	30.5
	F277L/D57Q	71.1 ± 0.4	99.2 ± 0.0	203

精准调控Baeyer-Villiger单加氧酶的底物选择性以避免拉唑亚砜的过氧化

Precise regulation of the substrate selectivity of Baeyer-Villiger monooxygenase to minimize overoxidation of prazole sulfoxides

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